Bizarre Protein That Influences Memory Behaves A Lot Like A Virus

There’s a lot about our genome, and how it was constructed and pieced together and altered over time that we don’t know about. In recent years, though, it’s become clear that silent stowaways have snuck aboard for the ride.

Once upon a time, these sneaky critters were viruses or virus-like ancestors – but somehow, they’ve managed to incorporate their genetic material into our own and become hidden passengers instead. Just last year, a brand new viral fragment was found in embryos and cancers; now, as reported in two new studies in Cell, a protein that’s vital for memory consolidation behaves an awful lot like a virus too.

The new research, spearheaded by the Universities of Utah and Massachusetts, came as quite the surprise to both teams.

They were examining Arc – a peculiar neuron-based protein that we suspect we need to form long-term memories. It also appears to ensure that brains remain “plastic”, which refers to their ability to rearrange themselves to optimize learning and cognitive processing. Without Arc, mice become amnesiacs.

Despite these revelations, much remains enigmatic about Arc, particularly with regards to its origins.

Upon closer inspection, these two research teams suddenly noticed that Arc appeared to be able to assemble sizeable structures. Most notably, it was seen producing a case that looked a lot like the protein shell of a virus, something known as a capsid, which protects the virus' genetic material.

Senior author Jason Shepherd – the assistant professor or neurobiology and anatomy at the University of Utah – told IFLScience that he was “blown away” when he first saw the capsid-like structures.

“I have been working on Arc all my career, since grad school, and this came completely as a surprise.”

Both of these characteristics can be found in modern-day retroviruses, like HIV or the human T-cell leukemia virus. Although they all act slightly differently, all retroviruses carry RNA – a cousin to DNA – and a special enzyme. Using said enzyme, they make a DNA copy of the RNA, and they use this copy to infect their host cells.

There's significance to the resemblence of Arc to retroviruses too, not just any old virus type: they're great at sneaking into animals.

“Many viruses can incorporate their DNA into the DNA of the host cell. However, retroviruses have become particularly good at integrating into germline,” Dr Ben Libberton, a microbiologist at the MAX IV Laboratory in Lund, Sweden, told IFLScience.

The germline, in simple terms, is a lineage of cells that pass DNA from generation to generation in an unbroken line.

Libberton, who wasn’t involved in the study, said that this “means that once they infect one person, their DNA has the potential to spread via sexual reproduction of the host.”

Of course, just because Arc walked and talked like a retrovirus, it doesn’t necessarily mean that’s what it once was. In order to be more certain, the team conducted a few novel experiments designed to see if Arc could “infect” cells like a real virus.

Indeed, they found that when the Arc capsids were given to brain cells of mice, the genetic material from within the capsid was transferred into the cells. A similar set of experiments in the Massachusetts-led paper on the common fruit fly found that genetic material transfer doesn’t just occur within neurons, but between neurons and muscles too.

So where did the original retrovirus for Arc come from? It’s likely that it emerged from retrotransposons, which are pieces of genetic material that can “jump” from site to site within genomes.

Credit: Jacobo Lopez, Yi-Chu Su, Hugo Vaca, University of Utah

Considered ancestral to modern retroviruses, the Utah team suspect that a retrotransposon leaped into an ancestor of ours 350-400 million years ago, which eventually morphed over time into Arc in humans. A similar process happened in flies 150 million years later.

So, Arc may be a virus-like remnant that helps control our memory – but that’s not the end of the story.

“What is the purpose of this RNA trafficking between cells, and what role does it play in memory formation?” Shepherd added. “Like most surprising observations, they end up posing more questions than answers – but we’re excited to follow this wild road!”

Either way, Arc isn't alone. "There are more than one hundred [retrovirus-like] genes in the human genome alone," the team add, but their specific roles remain an "open question."